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A microfiche appendix containing source code utilized in practicing an exemplary embodiment of the invention is included as part of the Specification and is hereinafter referred to as Appendix A. Appendix A includes a total of 2 microfiche and a total of 151 frames.
This invention relates in general to the field of neurology and neurological testing. More particularly, the present invention relates to the objective clinical assessment of motor function by computer analysis of a digitized writing sample, as may be used in the diagnosis and monitoring of motor disorders as well as the evaluation of motor development and handedness in children.
A patient may seek medical treatment for a variety of complaints which suggest a disturbance of motor function, such as weakness, stiffness, tremor, clumsiness, or difficulty in executing movements. It then is the physician""s responsibility to correctly diagnose the patient, and to implement the appropriate course of treatment. A number of syndromes which involve motor dysfunction exist, and are defined by their clinical manifestations.
For example, Parkinson""s Disease, which results from a degeneration of cells in the basal ganglia of the brain, is associated with slowness of movement (xe2x80x9cbradykinesiaxe2x80x9d), muscle rigidity, and a tremor often said to have a xe2x80x9cpill rollingxe2x80x9d quality which occurs at rest but tends to diminish with voluntary movements. In addition, patients suffering from Parkinson""s Disease may exhibit a loss of facial expression, a difficulty in initiating movements, and a diminution of their handwriting (xe2x80x9cmicrographiaxe2x80x9d).
Another fairly common motor disorder is essential tremor, an inherited condition which can present in childhood but more typically appears later in adult life. It usually involves the upper limbs, but may also affect the head, jaw, lips, tongue and pharynx. This tremor may abate upon ingestion of alcohol or beta-adrenergic antagonists. It may interfere with voluntary movements to the point where a sufferer is unable to drink from a glass or raise a spoon without spilling its contents.
There are numerous other motor disorders from hyperkinetic conditions such as essential tremor mentioned above to complex akinetic-rigid and other degenerative syndromes. Motor disorders may be considered primary when there are no known causes (other than genetics) and secondary, or symptomatic, when a known etiologic agent exists. Examples of primary motor disorders include Parkinson""s disease, essential tremor and adult onset focal dystonia such as writer""s cramp. Secondary motor disorders are more numerous and include Parkinsonian syndromes, side effects of medications such as tardive dyskinesia from neuroleptic use, immune, ischemic or even traumatic causes.
The multitude of motor disorders share many overlapping symptoms and signs. Even though sophisticated rating systems have been developed for some disorders (e.g., Parkinson""s Disease) to aid in the accuracy of diagnosis, in the hands of inexperienced practitioners, or where the disease is in its early stages and clinical signs are subtle, the potential for an erroneous diagnosis is substantial. Diagnosis by a traditional neurologic exam may also be difficult where the patient is unable to comply with fairly detailed instructions for tests used to evaluate motor function. As an example, a young child or a demented adult suspected of having a defect in motor development may be difficult to evaluate.
If an error in diagnosis is made, there may be significant adverse consequences. For example, the appropriate therapies for Parkinson""s Disease and essential tremor are very different, in that patients with Parkinson""s Disease are treated with agents that increase or facilitate dopamine activity whereas patients with essential tremor are treated with agents that block beta-adrenergic neurotransmitters. Not only would misdiagnosis result in a lack of a clinical benefit, but administering the inappropriate drug could have undesirable or even toxic side effects.
For example, beta adrenergenic blocking agents can adversely affect cardiac or pulmonary functions; unnecessary use in a Parkinson""s Disease patient, particularly an older patient, could be dangerous. Similarly, use of agents that treat Parkinson""s disease in a patient without that condition could have harmful consequences. Specific examples of Parkinson""s Disease treating agents include artane, sinemet and baclofen. Artane, an anticholinergic agent used to treat Parkinsonian tremors and dystonia can severely affect cognition, cardiac, visual and urinary function. Sinemet, a mainstay drug for Parkinson""s disease, causes nausea, vomiting, hallucinations and low blood pressure. Baclofen, an anti-spasmodic agent, and clonazepam, an anxiolytic and muscle relaxant, are used in many motor disorders but can alter mental status, blood pressure and can even be fatal when used inappropriately.
Further, even where the correct diagnosis has been made, it is important to be able to evaluate the clinical progress of a patient. Often the methods for measuring progress are extremely subjective.
One means by which clinicians have attempted to decrease subjectivity in diagnosis and monitoring motor function has been through the use of standardized clinical tests. Examples of such tests include asking the patient to touch his finger to, alternately, his nose and the outstretched finger of the examiner, or to run her heel up and down her shin, or to touch his or her thumb to, in succession, each of the other fingertips of the same hand.
Drawing has been used to evaluate motor function for many years. The famous neuropsychiatrist Kraepelin, at the beginning of this century, adapted an instrument to quantitatively analyze signatures for the evaluation of motor function in schizophrenic patients (Blyler et al., 1997, Schizophrenia Res. 26: 15-23, citing Hoch, 1904, Psychol. Bull. 1:241-257). One common test involves asking the patient to draw an Archimedes spiral. A thorough discussion of the spiral drawing test may be found in Bain and Findley, in xe2x80x9cStandards in Neurology, Series A: Assessment, diagnosis and evaluation, Book I: Assessing Tremor Severity,xe2x80x9d published by Smith Gordon and Co., Ltd., London, England/Nishimura Co., Ltd., Niigata-Shi, Japan, copies of which can be obtained in the United States through Books International Inc., Herndon, Virginia. According to that reference, the severity of tremor apparent in the spiral is rated from 0-10, where critical factors in determining the grade of a particular spiral are the degree of perpendicular displacement of the track from the intended trajectory and the extent to which tremor persists during each turn (Bain and Findley, p.9). Tremor is said to become more apparent in the outward turns of the spiral. An example of a study which used spiral analysis to quantify the effects of the drug terguride in Parkinson""s Disease patients is reported in Filipova et al., 1988, Eur. Arch. Psychiatr. Neurol. Sci.237:298-303. Another study which used spiral copying ability to evaluate the effect of the drug ondasetron on cerebellar tremor is described in Rice et al., 1997, J. Neurol. Neurosur. and Psychiat. 62:282-284.
A number of investigators have attempted to lessen the subjectivity of evaluation by using computer assistance. For example, Elble et al. (1996, Movement Disorders 11:70-78) asked patients with essential tremor to write a series of cursive e""s and l""s and, in some cases, to draw an Archimedes spiral on a digitizing tablet. They reported detecting changes in mean acceleration amplitude and tremor frequency with an accuracy which indicated that use of such a tablet was an accurate and less-costly alternative to accelerometry for tremor evaluation.
Wissel et al. (1996, J. Neurol. Neurosurg. and Psychiat. 61:172-175) used a digitizing tablet to measure writing speed in an evaluation of the effectiveness of botulinum toxin for treating writer""s cramp.
Eichorn et al., 1996, (Movement Disorders 11:289-297) used a computational analysis of open loop handwriting movements, as captured by a digitizing tablet, to monitor the effect of apomorphine on patients with early untreated Parkinson""s Disease. They reported that computer-assisted analysis of automated handwriting movements can be a quick method for quantifying dopamimetic effects on handwriting movements in parkinsonian patients. However, they also found that there was no statistically significant correlation when changes in the individual handwriting parameters were correlated with a subscore obtained using the Unified Parkinson""s Disease Rating Scale (xe2x80x9cUPDRSxe2x80x9d; Lang and Fahn, 1989, in xe2x80x9cQuantification of neurologic deficit,xe2x80x9d Munsat, ed., Butterworth-Heinemann, Storeham, Mass., pp. 285-309) for the writing hand, an observation which they indicated was expected, as the LPDRS assesses different kinds of parkinsonian symptoms, such as rigidity, akinesia, and tremor.
Blyler et al. (1997, Schizophrenia Res. 26: 15-23) used line drawing to measure lateralized motor performance in schizophrenic patients. The patients drew lines on a piece of paper, which were then scanned into a computer and a regression was run on the points of the line and used to calculate the deviation from straightness. The results were found to correlate with clinical rating scales of motor function, including the Simpsonxe2x80x94Argus Rating Scale (Simpson and Argus, 1970, Acta Psychiatr. Scand. 212 (Suppl.), 9-11) for parkinsonian symptoms.
Slavin et al., 1999, J. Internatl. Neuropsychol. Soc. 5:20-25, used a digitizing tablet to analyze writing samples from patients with dementia of Alzheimer""s type (xe2x80x9cDATxe2x80x9d). Kinematic measures of stroke length, duration, and peak velocity were expressed in terms of consistency via a signal-to-noise ratio. Patterns typical of DAT but not Parkinson""s disease were observed.
Lange-Kxc3xcttner (1998, Perceptual and Motor Skills 86:1299-1310) report that speeded drawing of basic graphic patterns by young children, as captured on a digitizing tablet, could be used to identify psychophysical problems.
Computational analysis of handwriting, for identification or analytical purposes, is described in Singer and Tishby, 1994, Biol. Cybern. 71: 227-237; van den Heuvel et al., 1998, Acta Psychologica 100: 145-159; and Morasso and Sanguineti, 1993, Acta Psychologica 82: 213-235.
In recent years the inventor has reported the use of a digitizing tablet and computer analysis of written spirals to evaluate motor disorders such as Parkinson""s Disease and essential tremor (Pullman et al., 1995, Neurology 45 (Suppl 4):A218 (abstract 208S); Yu et al., 1997, Society for Neuroscience Abstracts 23:abstract 737.8; Yu et al., 1998, Society for Neuroscience Abstracts 24:abstract 672.2). During this period of time, the inventor has been developing a method of producing a clinical rating which, unlike Eichorn""s measurements, correlates with the UPDRS score based on the computer analysis of handwritten spirals. This method is not described in any of the foregoing disclosures, but is disclosed herein.
The aforedescribed limitations and inadequacies of conventional systems and methods for analyzing movement disorders are substantially overcome by the present invention, in which a primary object is to provide a relatively inexpensive and non-invasive computerized system and method for clinically assessing motor function. Such a system and method can be adapted for analyzing movement disorders such as Parkinson""s disease, essential tremor and dystonia, and for characterizing neurological development and handedness in children.
In particular, the present invention relates to a computerized system and method for clinically assessing motor function comprising correlating geometric indices, computed from digital information obtained from a geometric shape drawn by a subject to be evaluated, with a clinical rating score derived using a xe2x80x9cstandard of referencexe2x80x9d generated by one or more clinical expert. By analogy to a biochemical assay, which measures the amount of reactant by comparison to a standard curve, the present invention provides a method and system by which a medical practitioner can evaluate the motor function of a subject by generating a digitized writing sample and computationally comparing geometric indices obtained therefrom with values associated with clinical ratings assigned by skilled neurologists. Interpretation is thereby rendered more objective and consistent. Furthermore, the test may be administered and interpreted by physicians who are not skilled or experienced in evaluating motor disorders, for example general practitioners or pediatricians who are not specialized in the practice of neurology. The present invention therefore provides a means for evaluating persons early in the course of disease, and for screening patients for motor dysfunction or, in the case of children, disorders of motor development.
Hence, in accordance with a first aspect of the present invention, a system for clinically assessing motor function in a subject is provided that includes: an electronic digitizing tablet having a writing device for obtaining a geometric pattern handwritten by the subject and providing one or more digital signals representing the pattern; and a microprocessor for processing the signals to derive one or more geometric indices representative of motor function and for computing from the indices, using the aforementioned expert-generated xe2x80x9cstandard of referencexe2x80x9d, a clinical rating score indicative of motor function of the subject.
In another aspect of the present invention, a preferred method for analyzing movement disorders includes: a method for clinically assessing motor function in a subject comprising: obtaining a geometric pattern handwritten by the subject on a digitizing tablet; generating one or more digital signals representing the geometric pattern; processing the signals to derive one or more geometric indices representative of motor function; and computing from the geometric indices, using the aforementioned expert-generated xe2x80x9cstandard of referencexe2x80x9d, a clinical rating score indicative of motor function of the subject.
Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the invention.